Single photon emission computed tomography, SPECT, allows the measurement of the 3-D distribution of radioactive tracers in brain. Tracers in use fall into two main classes. In the first class, the tracer is taken up in brain in proportion to blood flow and thus can be utilized as a marker of neural activity. The second class of tracers binds to sites in brain such that the activity then reflects the distribution of the related neurochemistry. Previous work focused on the use of Xenon-133 and Xenon- 127 for absolute flow measurements during cognitive activation tasks. This work was extended to perfusion related tracers using Tc-99m to determine their ability for rCBF measurements using dose normalization and split dose activation paradigms. While this work was largely successful, other more sensitive means exist for CBF measurements leaving us to concentrate on the use of SPECT for neurochemistry. Neurochemistry studies have involved IQNB, a muscarinic receptor antagonist, and IBZM, a D2 dopamine receptor antagonist. SPECT IQNB scans demonstrated focal areas of reduced uptake in patients with dementia. Current studies involve using IQNB scans demonstrated focal areas of reduced uptake in patients with dementia. Current studies involve using IQNB to determine if receptor up-regulation Is possible in a clinical population. We have compared normal controls with Alzheimer patients on both perfusion scans and IQNB after chronic low dose scopolamine. The difference in groups was marked when comparing the ratio I-QNB to HMPAO uptake, indicating a double dissociation and suggesting a differential sensitivity to chronic cholinergic blocade. Use of IBZM in normal volunteers and in Parkinson's Disease patients with clinical asymmetrical presentation appear to provide a sensitive measure of clinically meaningful dopamine function. Studies in schizophrenic patients treated with clozapine have shown a curvilinear relation between blood level and estimated D2 receptor occupancy. Initial studies aimed at examining the relation between dopaminergic measures and clinical symtomatology in schizophrenic patients have indicated a good degree of correlation and appear very promising. Major results have been established with several compounds. IOXY is a potential agent for opiate receptor imaging, blockade and displacement studies have indicated specific binding rather than flow related activity. Another class of compounds had demonstrated selective imaging of sigma receptor subtypes. Another aspect of radio ligand development is the ease of preparation of the agents involved. Previously IQNB uses had been hampered by low radio chemical yield, long reaction time and high cost. A tin derivative method has been developed that gives a high yield of isomerically and radiochemically pure 1-123-IQNB in a short reaction time.